An experimental model has been established to study the regulatory role of retinoids in growth and differentiation. Retinoid deprivation during embryonal development of the chick and quail causes abnormalities in organs of epithelial and mesenchymal origin, most dramatically preventing the formation of the extraembryonal circulatory system. By light microscopy, TEM and SEM, retinoid-deficient quail embryos (5 somite stage to 2 days of age) show the following sequence of events leading to vascular abnormalities: 1) a cardia bifida forms if development of the heart is retarded before fusion of the primitive endothelial heart tubes takes place; 2) a single enlarged ventricle develops in situ inversoif retardation manifests itself at a later stage; and 3) in all cases, the omphalomesenteric veins that normally extend caudal from the sinus venosus are not developed and the endocardium of the heart terminates as a blind pouch in the mid-ventral region of the animal. The results thus provide evidence for the failure to establish, at the level of the omphalomesenteric veins, a connection between the embryonal and extraembryonal circulatory system in the retinoid-deficient quail embryos. Since the extracellular matrix is of importance in normal cell growth, cell movement and differentiation, and thus may be a decisive factor in coordinated differentiation of the heart in the early embryo, we are testing the role of matrix proteinss such, as fibronectin and laminin, in early development using our model system of the retinoid-deficient quail embryo. These studies are now extended to evaluate the role of growth factors, especially TGF-B, in cell growth and differentiation.